Skip to main content
SpringerLink
Log in

Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin‑2 and nectin‑4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin‑2 and nectin‑4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin‑2 and nectin‑4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin‑2 was found superior to both serum nectin‑4 and serum nectin-2 + nectin‑4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin‑2 and nectin‑4 might be used in lung cancer diagnosis but the diagnostic importance of nectin‑2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2018;68:7–30.

    Article  PubMed  Google Scholar 

  3. Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, et al. Alectinib in Crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34:661–8.

    Article  CAS  PubMed  Google Scholar 

  4. Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55–52.

    Article  CAS  PubMed  Google Scholar 

  5. Besse B, Adjei A, Baas P, Meldgaard P, Nicolson M, Paz-Ares L, et al. Panel Members; ESMO. 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014;25:1475–1474.

    Article  CAS  PubMed  Google Scholar 

  6. Takai Y, Miyoshi J, Ikeda W, Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol. 2008;9:603–15.

    Article  CAS  PubMed  Google Scholar 

  7. Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y. The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol. 2007;19:593–592.

    Article  CAS  PubMed  Google Scholar 

  8. Yamada A, Fujita N, Sato T, Okamoto R, Ooshio T, Hirota T, et al. Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells. Oncogene. 2006;25:5085–5082.

    Article  CAS  PubMed  Google Scholar 

  9. Morita H, Nandadasa S, Yamamoto TS, Terasaka-Iioka C, Wylie C, Ueno N. Nectin‑2 and N‑cadherin interact through extracellular domains and induce apical accumulation of F‑actin in apical constriction of Xenopus neural tube morphogenesis. Development. 2010;137:1315–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamada A, Irie K, Fukuhara A, Ooshio T, Takai Y. Requirement of the actin cytoskeleton for the association of nectins with other cell adhesion molecules at adherens and tight junctions in MDCK cells. Genes Cells. 2004;9:843–55.

    Article  CAS  PubMed  Google Scholar 

  11. Nakanishi H, Takai Y. Roles of nectins in cell adhesion, migration and polarization. Biol Chem. 2004;385:885–882.

    Article  CAS  PubMed  Google Scholar 

  12. Reymond N, Fabre S, Lecocq E, Adelaïde J, Dubreuil P, Lopez M. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem. 2001;276:43205–15.

    Article  CAS  PubMed  Google Scholar 

  13. Fabre S, Reymond N, Cocchi F, Menotti L, Dubreuil P, Campadelli-Fiume G, et al. Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C‑C′-C″-D beta-strands of the nectin1 V domain. J Biol Chem. 2002;277:27006–13.

    Article  CAS  PubMed  Google Scholar 

  14. Matsushima H, Utani A, Endo H, Matsuura H, Kakuta M, Nakamura Y, et al. The expression of nectin-1alpha in normal human skin and various skin tumours. Br J Dermatol. 2003;148:755–62.

    Article  CAS  PubMed  Google Scholar 

  15. Athanassiadou AM, Patsouris E, Tsipis A, Gonidi M, Athanassiadou P. The significance of Survivin and Nectin‑4 expression in the prognosis of breast carcinoma. Folia Histochem Cytobiol. 2011;49:26–33.

    Article  CAS  PubMed  Google Scholar 

  16. Derycke MS, Pambuccian SE, Gilks CB, Kalloger SE, Ghidouche A, Lopez M, et al. Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am J Clin Pathol. 2010;134:835–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fabre-Lafay S, Monville F, Garrido-Urbani S, Berruyer-Pouyet C, Ginestier C, Reymond N, et al. Nectin‑4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer. 2007;7:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Takano A, Ishikawa N, Nishino R, Masuda K, Yasui W, Inai K, et al. Identification of nectin‑4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res. 2009;69:6694–703.

    Article  CAS  PubMed  Google Scholar 

  19. Karabulut M, Gunaldi M, Alis H, Afsar CU, Karabulut S, Serilmez M, et al. Serum nectin‑2 levels are diagnostic and prognostic in patients with colorectal carcinoma. Clin Transl Oncol. 2016;18:160–71.

    Article  CAS  PubMed  Google Scholar 

  20. Son Y, Lee B, Choi YJ, Jeon SA, Kim JH, Lee HK, et al. Nectin‑2 (CD112) is expressed on outgrowth Endothelial cells and regulates cell proliferation and Angiogenic function. PLoS ONE. 2016; https://doi.org/10.1371/journal.pone.0163301.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR‑2 internalization and signaling from intracellular compartments. J Cell Biol. 2006;174:593–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, et al. Nectin‑2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol. 2013;6:179–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Liang S, Yang Z, Li D, Miao X, Yang L, Zou Q, et al. The clinical and pathological significance of Nectin‑2 and DDX3 expression in pancreatic ductal Adenocarcinomas. Dis Markers. 2015; https://doi.org/10.1155/2015/379568.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Izumi H, Hirabayashi K, Nakamura N, Nakagohri T. Nectin expression in pancreatic adenocarcinoma: nectin‑3 is associated with a poor prognosis. Surg Today. 2015;45:487–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kawanishi A, Hirabayashi K, Yamada M, Takanashi Y, Hadano A, Kawaguchi Y, et al. Clinicopathological significance of Necl‑4 expression in pancreatic ductal adenocarcinoma. J Clin Pathol. 2016; https://doi.org/10.1136/jclinpath-2016-204028.

    Article  PubMed  Google Scholar 

  26. Jang SM, Han H, Jun YJ, Jang SH, Min KW, Sim J, et al. Clinicopathological significance of CADM4 expression, and its correlation with expression of E‑cadherin and Ki-67 in colorectal adenocarcinomas. J Clin Pathol. 2012;65:902–6.

    Article  CAS  PubMed  Google Scholar 

  27. Maniwa Y, Nishio W, Okita Y, Yoshimura M. Expression of nectin 3: novel prognostic marker of lung adenocarcinoma. Thorac Cancer. 2012;3:175–81.

    Article  PubMed  Google Scholar 

  28. Lattanzio R, Ghasemi R, Brancati F, Sorda RL, Tinari N, Perracchio L, et al. Membranous Nectin‑4 expression is a risk factor for distant relapse of T1–T2, N0 luminal—A early breast cancer. Oncogenesis. 2014; https://doi.org/10.1038/oncsis.2014.32.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, et al. Enfortumab Vedotin antibody-drug conjugate targeting Nectin‑4 is a highly potent therapeutic agent in multiple Preclinical cancer models. Cancer Res. 2016;76:3003–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Oncology, Istanbul University, Capa, 34093, Fatih, Istanbul, Turkey

    Kayhan Erturk, Sule Karaman, Nergiz Dagoglu, Murat Serilmez, Derya Duranyildiz & Faruk Tas

Authors
  1. Kayhan Erturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sule Karaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nergiz Dagoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Murat Serilmez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Derya Duranyildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faruk Tas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kayhan Erturk.

Ethics declarations

Conflict of interest

K. Erturk, S. Karaman, N. Dagoglu, M. Serilmez, D. Duranyildiz and F. Tas declare that they have no conflict of interest relating to the publication of this manuscript.

Ethical standards

K. Erturk, S. Karaman, N. Dagoglu, M. Serilmez, D. Duranyildiz, and F. Tas declare that the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study. Regional Ethics Committee and Number: Istanbul University, Institute of Oncology Regional Ethics Committee; Number: 2015/321.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erturk, K., Karaman, S., Dagoglu, N. et al. Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?. Wien Klin Wochenschr 131, 419–426 (2019). https://doi.org/10.1007/s00508-019-01537-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-019-01537-4

Keywords

Search

Navigation